As a result of ozone depletion by chlorofluorocarbons the elimination of these compounds has been proposed and replacements are being sought. The addition of hydrogen atoms to the chlorofluorocarbon molecules should allow substantial degradation of these compounds in the lower atmosphere, with little depletion of stratospheric ozone. HCFC-123 (2,2-dichloro-1,1,1-trifluoroethane) is a compound currently under investigation as a chlorofluorocarbon replacement. Because of its structural similarity with halothane (2-bromo-2-chloro-1,1,1,-trifluoro- ethane), we investigated the metabolism of HCFC-123 in male Fischer 344 rats. Rats were placed in inhalation chambers. Group 1 received air for 2 hours, group 2, 1.3% halothane for 2 hours, while groups 3 and 4 received 1.1% and 0.7% HCFC-123, respectively, for 2 hours. All rats were killed 15 hours post-exposure and liver microsomal and cytosol fractions were prepared. Following sodium dodecyl sulfate polyacrylamide gel electrophoresis, constituent polypeptides from each fraction were transferred to nitrocellulose membranes and probed with hapten specific anti-trifluoroacetyl protein serum. Both compounds were found to produce identical patterns and similar levels of trifluoroacetylated proteins in both fractions, with the microsomal fraction showing the highest level of trifluoroacetylated proteins. This finding raises the possibility that susceptible individuals repeatedly exposed to HCFC-123 may become sensitized and develop hepatitis similar to that produced by halothane.